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地中海实验室
Chemical Synthesis, Bioinorganic Chemistry and Polymer Chemistry
教授: 克里斯蒂娜·库利博士.D.
概述:
研究 in the Cooley lab applies the power of synthetic organic chemistry to solve problems in biology and human health. Students in my lab will have the opportunity to design and synthesize new molecules and assess their ability to detect and treat human 疾病 under the following two major project areas.
Our primary research area is in the development of new methods to amplify molecular signals as a way to detect biomolecular interactions and potentially, 疾病. We have developed fluorogenic monomers that are not fluorescent in monomer form, but glow when incorporated into a polymer synthesized by various methods, 例如原子转移自由基聚合(ATRP). Polymer fluorescence is quantifiable by fluorescence readers or visible to the naked eye, and tracks with the concentration of polymerization initiator, 哪个服务于模型分析人员.
This fluorogenic polymerization subgroup has many current research directions ranging from fundamental organic synthesis and polymerization studies to detection applications. Current projects are aimed toward the synthesis of new monomers to improve physical properties such as water solubility, development and evaluation of alternative light-initiated fluorogenic polymerization platforms, optimization of the fluorogenic polymerization approaches for analyte detection, and application to the direct detection of proteins and biomolecular interactions. 在这个领域工作的学生将应用一系列有机, 高分子与生化技术, from the chemical synthesis of small molecules and free-radical polymerization techniques initiated by various methods from metal catalysts to irradiation with visible light, to analysis and characterization of the polymers formed by gel permeation chromatography, 核磁共振波谱学, 荧光分析方法.
The Cooley lab has a second subgroup in the general field of therapeutic drug delivery, utilizing the sensing of reactive oxygen species (ROS) for prodrug activation and therapeutic release in 疾病d tissues. A prodrug is a “caged” version of a drug that is inactive until release to the free drug is achieved under specific biological conditions. 我们合成并评价了AA 147的前药, which activates a stress-responsive signaling pathway as a therapeutic target for treatment following reperfusion events such as heart attacks and strokes. These prodrugs of AA 147 are selectively uncaged by the presence of reactive oxygen species (ROS), 哪些在再灌注事件中高水平发生. We are also exploring other types of releasable AA 147 prodrugs to improve pharmacodynamics properties for in vivo animal studies, and the synthesis of fluorogenic ROS sensors for collaborative chemical applications. Students in this area will gain experience with small-molecule synthesis and characterization, and analyze their therapeutic release profile under biological conditions.
兰伯特实验室
有机化学
Amber is the fossilized end product of resinous materials exuded by plants millions of years ago. 除了南极洲，它在每个大陆都有. 琥珀至少有五种化学性质不同的类型, depending on the botanical material from which the original exudate came from. Nuclear magnetic resonance (NMR) spectroscopy can distinguish these different botanical sources and provide a means of determining authenticity of amber and learning about its geographical sources.
更一般的, exudates are complex mixtures of organic compounds produced by plants, 通常是受伤或疾病的结果. Secreted as liquids, exudates may harden to solids in hours to months on the surface of the plant. These materials have found numerous practical applications throughout human history, and they provide a molecular window to the classification of plants (taxonomy). We have found that exudates are remarkably robust and consistent in their molecular constitution within a single plant and from plant to plant within a given species. There are several, distinct chemical constitutions of exudates. Resins, which can form amber through fossilization, are composed of terpenoid compounds. 树胶是由多糖构成的. Gum resins like frankincense and myrrh contain both materials. 基诺含有酚类物质. 虽然这四个化学基团是最大的, there are several other smaller but distinct chemical groups.
We are carrying out a worldwide survey of plant exudates from all plant families, 还有琥珀, necessitating field acquisition of materials and analysis by NMR in the lab. We also are examining the effect of heat on the molecular structure of amber and its slightly younger colleague, 柯巴脂. Heat has been used to alter the properties of amber prior to carving. Spectroscopic examination of artificially heated samples may clarify how structure change with heating.
希勒实验室
Bioinorganic Chemistry; Computational Chemistry; X-ray Spectroscopy
类型: 无机化学
教授: Jason Scherer博士.D.
研究 in the 希勒集团 is broadly centered on understanding how the electronic structure of biologically and industrially relevant transition metal species contribute to their reactivity and physical properties. Central to our work is the synergistic use of synthetic, spectroscopic and computational chemistry. Although we perform some work with naturally occurring biological systems or industrial catalysts, we primarily study synthetic mimics of these systems to probe a specific aspect of their chemistry. Briefly outlined below are two projects currently being undertaken by the 希勒集团.
1. 探测含镍超氧化物歧化酶. Nickel containing superoxide dismutase (NiSOD) catalyzes the conversion of highly toxic superoxide (O2–) into dioxygen and hydrogen peroxide by making use of a NiII/NiIII redox couple. In the reduced NiII oxidation state the nickel-site is contained in a distorted square planar NiN2S2 coordination environment with ligands derived from Cys2, Cys6, the N-terminal amine nitrogen and an amidate nitrogen from Cys2. An unusual feature of the NiSOD active site that we have been probing is the fact that one of the coordinated Cys sulfur ligands is protonated, 形成Ni-S(H+)-Cys基团. A number of roles for this moiety can be envisioned; our hypothesis is that protonation of the Cys sulfur ligand poises the nickel site for reactivity. We postulate that protonation raises the energy of orbitals that are predominantly nickel in character allowing for electron transfer from NiII to O2–, 从而产生O22 -(过氧化物)和NiIII. 为了验证这个假设, we are preparing a number of metallopeptide based mimics of NiSOD along with small transition metal complexes that can support reversible Ni-S(H+)-Cys formation. By spectroscopically examining the influence of sulfur protonation in such mimics, we seek to understand the role(s) of the Ni-S(H+)-Cys moiety in NiSOD reactivity, 和一般含Ni-S-R的化合物.
2. Understanding Transition Metal Ligand Bonds Through the Lens of Valence Bond Theory. In modern chemical physics quantum mechanical descriptions of chemical bonding are described through three main models: molecular orbital, 密度泛函, 和价键(VB)理论. All of these approaches have distinct benefits and disadvantages. VB theory has the advantage of placing bonding in terms that chemists understand (covalent vs ionic bonding), 这就产生了对化学键的直观描述. 然而, it has only been in the past decade that VB theory methods have advanced to the point where larger systems of chemical interest can be tackled at a sufficiently high level of theory to yield accurate solutions. We have taken advantage of these recent advances in VB theory to explore the bonding, 能量, and reactivity of transition metal complexes involved in organometallic transformations. 例如, we have recently investigated reductive elimination from [CuR4]– complexes (R = alkyl) and discovered a number of “hidden” features concerning the chemistry of such species. 例如, one surprising aspect of such reactions is that they are not reductive eliminations in any physically meaningful sense of the word; instead they can be viewed as admixtures of radical C-C couplings and simple Lewis acid/base reactions.
Urbach集团
Supramolecular Chemistry; Biosensing; Diagnostics; Drug Formulation
网站: Urbach集团
教授: 亚当·厄巴赫博士.D.
The chemistry of pharmaceuticals and medical diagnostics is designed to recognize a specific protein in a complex mixture, 比如血, 然后粘在蛋白质上. 药物阻断了这种蛋白质的正常功能. 医学诊断测量的是这种蛋白质的数量. The Urbach lab develops new chemistry for the recognition of specific proteins, and we use this chemistry to solve important biomedical problems. Students are involved in experimental design and implementation, 解决问题, 数据分析, 演讲, 和出版.
Students in the Urbach research group learn a range of techniques, 其中包括有机合成来制造多肽, 物领域, 水凝胶, and modified proteins; NMR spectroscopy; mass spectrometry; microcalorimetry; fluorescence spectroscopy; circular dichroism spectroscopy; and X-ray crystallography. This combination of methods and approaches offers students a breadth of technique and depth of study that is an excellent foundation for further study in organic chemistry, 生物物理化学, 药物化学, 生物化学, 生物工程, 和生物技术.
Current projects include: 1) Developing new chemistry to recognize proteins and proteins on the basis of their amino acid sequences. Our discoveries have established new rules for predictive protein recognition, and we are currently working to expand the range of proteins that are accessible by our compounds, 并增加相互作用的强度和选择性. 2)合成具有新性质的新蛋白受体. 3) Developing technology for the quality control of protein drug formulations. 4) Developing a new strategy for protein drug formulation that enables controlled time release. Dr. Urbach is always interested in discussing new ideas with students. These projects are funded by grants from the National Institutes of Health and the Welch Foundation.